Project Summary: Dry eye (DE), characterized by a myriad of signs (e.g. decreased tear production, increased evaporation, and inflammation) and symptoms (e.g. pain, blurry vision and dryness), is a debilitating disease that affects quality of life. Many patients have persistent symptoms, because the available clinical therapies are not adequate to manage DE. Thus, managing DE requires solutions (i.e. beyond individual- level clinical interventions). An emerging literature suggests that environmental conditions can contribute to the onset and persistence of DE. Our microenvironment is a complex mixture of particulate matter (PM), gaseous air pollutants and allergens. However, individual specific data on microenvironment are not available. The project will test two novel hypotheses: 1) the clinical manifestations, measured by the types and severity of different measures of DE, vary with respect to types, levels and sources of air pollutants, allergens, humidity and temperature, specifically, exposure to PM, bioaerosols and gaseous pollutants is associated with epithelial disruption (ED), inflammation and evaporative tear deficiency (ETD), respectively; 2) DE signs are more strongly associated with indoor relative to outdoor air pollution, as we spend more time indoors and our indoor exposure dominates our total exposure to microenvironmental conditions. To test these hypotheses, we propose a prospective case-control design. We will recruit 360 subjects from Bascom Palmer Eye Institute (BPEI), ranked as the number 1 eye institute in the US consecutively for the past 12 years, and University of Maryland Ophthalmology ? Redwood (UMOR) clinics. 180 cases and age-, gender- and race/ethnicity-matched 180 controls will be determined after their clinical exams. Subjects who meet the inclusion criteria and have at least one of the three measures of DE, namely ED, inflammation, and ETD, will serve as cases, and controls will be free from these DE signs, and will meet inclusion criteria. Each subject will undergo four clinical exams one in each of the four seasons, and a weeklong intensive air pollution monitoring inside and outside their homes before the clinical exam. PRECISE (precise.ccs.miami.edu), our portable battery of direct-reading sensors, will measure air pollution in each subject's home for one full year. Over the same week, participants will record DE symptoms through web or phone. We will calculate time- weighted indoor and outdoor exposures, and model the effects of exposure on DE signs and symptoms using spatial econometric models. Our interdisciplinary team has the state-of-the-art laboratory facilities for clinical assessment of DE and exposure assessment as well as a collaborative track-record over four years. This project will generate knowledge that will potentially provide a new line of home-based environmental treatment to manage DE. This research aligns with the ?ocular infection, inflammation and immunology? priority areas of the National Eye Institute (NEI).